We recently engaged with the systematic review by Soheilipour et al.[1], concludes that Akkermansia muciniphila primarily acts as a pathobiont in colorectal cancer (CRC) by exacerbating tumor progression. While the authors provide a comprehensive analysis of the bacterium's pathobiont potential (particularly its propensity to exacerbate colitis-associated tumorigenesis by degrading mucins in inflamed environments) we wish to underscore a pivotal therapeutic evolution: the transition from live probiotics to targeted postbiotics (defined as non-viable bacterial products or metabolic byproducts that confer a health benefit to the host).

Emerging evidence indicates that the functional role of A. muciniphila is highly context-dependent [2]. In "susceptible clinical settings," such as inflamed environments or post-antibiotic contexts where the microbiome is depleted, live A. muciniphila may lead to excessive mucin degradation [1]. This erosion of the mucus layer can compromise intestinal barrier integrity, allowing for increased translocation of pro-inflammatory factors and promoting inflammation-driven tumorigenesis. Consequently, for CRC patients (who often present with pre-existing dysbiosis and epithelial dysfunction) the administration of live strains carries a significant risk-to-benefit ratio [1,2].

In contrast, individual molecular components of A. muciniphila reliably exhibit anti-tumorigenic properties without the risk of barrier disruption [2]. For instance, the outer membrane protein Amuc_1100 has been demonstrated to attenuate tumorigenesis by activating cytotoxic T lymphocytes (CTLs) [3]. Furthermore, the recently characterized acetyltransferase Amuc_2172, delivered via extracellular vesicles, has been shown to epigenetically reprogram the tumor microenvironment, thereby enhancing the efficacy of PD-1 blockade [4].

These findings suggest that the future role of A. muciniphila in oncology should pivot away from effective colonization and instead focus on the precision application of its bioactive molecules. We advocate for future clinical trials to prioritize these postbiotic derivatives (Amuc_1100, Amuc_2172, and extracellular vesicles) in order to exploit the immunological benefits of the bacterium while mitigating its pathobiont liabilities.

Conflict of interest

There is no conflict of interest.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Authors' contributions

All authors contributed equally to all stages of the article, including the conception and design of the study, acquisition, analysis, and interpretation of data, drafting and revising the manuscript, and final approval of the version to be published.

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Declaration of generative AI and AI-assisted technologies in the writing process

During the preparation of this work the authors used Perplexity, Grammarly, and Gemini in order to translate, increase clarity, and proofing. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.